Mechanisms of Axon Injury in Multiple Sclerosis
The goal of the lab's research into mechanisms of axon injury in multiple sclerosis is to characterize pathogenic cascades that can be therapeutically targeted to preserve function in patients with multiple sclerosis.
Loss of axons as a result of demyelination is the principal cause of progressive loss of neurological function in patients with multiple sclerosis.
Dr. Howe's lab is testing the novel hypothesis that demyelinated axons are injured by a specific arm of the immune system that is not targeted by currently available therapies. The lab's intention is to design new molecular and cellular strategies for preventing this immune-mediated axon injury, thereby preserving function and preventing irreversible injury in patients with multiple sclerosis.
Focus areas include:
- Discovering the molecular mechanisms involved in making demyelinated axons susceptible to attack by cytotoxic (CD8+) T cells
- Using high-resolution live cell imaging and proteomics to determine the injury mechanisms engaged within demyelinated axons during the CD8+ T cell-mediated attack
- Characterizing the role of CD8+ T cells in the injury of demyelinated axons within the optic nerve in several animal models of multiple sclerosis
- Using neurons derived from induced pluripotent stem cells from humans and patient-specific CD8+ T cells to identify the anti-axonal T cells responsible for loss of function in patients with multiple sclerosis
- Identifying the inflammatory factors — produced by glial cells in response to demyelination — that drive direct and indirect axonal injury
- Developing new microfluidic chambering devices for the biochemical, transcriptional, proteomic and metabolic interrogation of isolated axons